INHIBITION OF LYSOPAF ACETYLTRANSFERASE ACTIVITY BY FLAVONOIDS

Objective and Design. Several kinds of flavonoids, widely distributed natural products of the vegetable kingdom which possess anti-inflammat ory activity, were examined for inhibitory effects on the acetyl-CoA: 1-alkyl-2-lyso-sn-glycero-3-phosphocholine (lysoPAF) acetyltransferase activity. Methods: Acetyl-CoA:lysoPAF acetyltransferase activity was determined using homogenates of a rat mucosal-type mastcytoma cell lin e, RBL-2H3 as an enzyme source. The production of platelet-activating factor (PAF) in rat peripheral white blood cells stimulated with the c alcium ionophore A23187 was studied. Results: Of the flavonoids tested , luteolin and quercetin exhibited significant inhibitory effects (IC5 0, 45 mu M and 80 mu M, respectively), whereas other structurally-rela ted flavonoids failed to affect the lysoPAF acetyltransferase activity . Luteolin did not suppress the activity of choline acetyltransferase, suggesting that the inhibition observed here was specific. Luteolin a lso inhibited the production of PAF in rat peripheral white blood cell s. Conclusions: These results indicate that luteolin could become a le ading compound for developing a novel type of anti-inflammatory, anti- allergic drugs that target lysoPAF acetyltransferase.